A mechanism by which peptide hormones and neurotransmitters regulate the vigor of immunity is proposed. Lymphocyte activation stimulates a rapid DNA independent emergence then loss of insulin receptors. Pilo studies show that resting T cells but not B cells or macrophages bear cholinergic and beta-adrenergic binding units. T cell activation results in reciprocal dynamic changes in cholinergic and beta-adrenergic binding rendering early, but not late, killer T cells sensitive to cholinergic amplification signals and late, but not early, killer T cells sensitive to beta-adrenergic depressive signals. That lymphocyte activation triggers dynamic, preprogrammed changes in lymphocyte subset receptiveness to neurotransmitters and hormonal agents will be directly assessed by studying resting and activated purified lymphocyte subsets (suppressor cells, cytotoxic cells, and helper cells) for sensitivity to functional changes produced by hormones and neurotransmitters and for changes in the distribution, concentration and affinity of receptor binding units. A novel flow cytometric technique will allow isolation of cells that bear acetylcholine adrenergic, insulin, and histamine receptor bearing cells in order to examine their Ly phenotype and function. We propose to study a system, whose existence is suggested by pilot studies, in which positive and negative neuroendocrine loops, acting in concert with immunoregulatory lymphocytes, facilitate the initiation and then aid in dampening the terminal phase of immune responses. The existence of neuroendocrine regulation of immunity will be tested in healthy and diabetic animals to probe a possible defect in insulin-lymphocyte receptor interactions.